p53 is the most commonly inactivated gene in human cancer and loss of critical p53 pathways are central to tumorigenesis1,2. The p53 protein binds specific DNA sequences and transcriptionally activates responsive genes. p53 gene mutations that occur in human cancer produce abnormal p53 proteins that are unable to bind DNA and promote the transcription and modulation of its target genes3. Furthermore, mutant p53 protein can act in a dominant negative manner by disturbing the function of wild type p53 protein and its ability to regulate cell proliferation4,5. p53 mutant protein also heterodimerizes with wild type p53 and results in a conformational change of the protein that no longer binds to p53 regulating cis-elements6,7.
There is a continuing need in the art for a more complete understanding of the components of the pathways in which p53 acts. Moreover, there is a continuing need for improved diagnostic and therapeutic methods for treating cancers.